PT  - JOURNAL ARTICLE
AU  - Christopher K. Salmon
AU  - Tabish A. Syed
AU  - J. Benjamin Kacerovsky
AU  - Nensi Alivodej
AU  - Alexandra L. Schober
AU  - Michael T. Pratte
AU  - Michael P. Rosen
AU  - Miranda Green
AU  - Adario DasGupta
AU  - Hojatollah Vali
AU  - Craig A. Mandato
AU  - Kaleem Siddiqi
AU  - Keith K. Murai
TI  - Organizing Principles of Astrocytic Nanoarchitecture in the Mouse Cerebral Cortex
AID  - 10.1101/2021.11.05.467391
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.05.467391
4099  - http://biorxiv.org/content/early/2021/11/05/2021.11.05.467391.short
4100  - http://biorxiv.org/content/early/2021/11/05/2021.11.05.467391.full
AB  - Astrocytes have complex roles in central nervous system (CNS) health and disease. Underlying these roles is an elaborate architecture based on frequent, extremely fine, but seemingly haphazard branches, as well as prominent features including tripartite synaptic complexes and perivascular endfeet. While broad categories of structures in astrocytes are known, the fundamental building blocks that compose them and their organizing principles have yet to be adequately defined. This is largely due to the absence of high-resolution datasets that can reveal nanoscopic features of astrocytes (i.e. 10-20nm diameter in x, y, and z) and a lack of computational approaches that can effectively interrogate astrocyte shape, organization, and nanoarchitecture. Here, we produced and analyzed multiple, high-resolution datasets of layer 2/3 mouse somatosensory cortex using focused ion beam scanning electron microscopy (8nm intervals) and computer vision approaches to provide a principled, quantitative analysis of astrocytic nanoarchitecture. A decomposition of astrocytes into fundamental ‘parts’ led to the discovery of unique structural components, recurring structural motifs, and assembly of parts into an organized hierarchy. New relationships were also discerned between astrocytic processes and other CNS microanatomy including mitochondria, tripartite synapses, and cerebrovasculature. By deploying computational resources to quantitatively understand the organizing principles and nanoarchitecture of astrocytes, this study reveals the specialized anatomical adaptations of these complex cells within the CNS.One Sentence Summary Using high-resolution serial electron microscopy datasets and computer vision, this study provides a systematic analysis of astrocytic nanoarchitecture from multiple samples of layer 2/3 of adult mouse neocortex, and presents quantitative evidence that astrocytes organize their morphology into purposeful, classifiable assemblies with unique structural and subcellular organelle adaptations related to their physiological functions.Competing Interest StatementThe authors have declared no competing interest.